Cognitive fatigue in relation to depressive symptoms after treatment for childhood cancer.
ABSTRACT: BACKGROUND:Cognitive fatigue after childhood cancer is frequently overlooked despite guidelines recommending follow-up, and might be mistaken for depression due to overlapping symptoms. Our objectives were: 1) to examine ratings of fatigue in survivors of paediatric brain tumours (BT) and acute lymphoblastic leukaemia (ALL) compared to healthy controls, 2) to examine the relationship between symptoms of depression and cognitive fatigue, and 3) to evaluate parent-child concordance in ratings of cognitive fatigue. METHODS:Survivors of BT (n?=?30), survivors of ALL (n?=?30), and healthy controls (n?=?60) aged 8-18?years completed the Pediatric Quality of Life Multidimensional Fatigue Scale and the Beck Youth Inventories. Associations between cognitive fatigue, diagnosis and depression were assessed with general linear modelling. Group differences were analysed using the Kruskal-Wallis test. Parent-child concordance was investigated with internal consistency reliability. RESULTS:Cognitive fatigue was prevalent in 70% of survivors of BT survivors and in 30% of survivors of ALL. Diagnosis was the main predictor of cognitive fatigue (p?
Project description:BACKGROUND:Little is known about longitudinal symptom burden, its consequences for well-being, and whether lifestyle moderates the burden in older survivors. METHODS:The authors report on 36-month data from survivors aged ?60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self-reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]-Fatigue scale), cognitive (on the FACT-Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State-Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well-being was measured using the FACT-General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. RESULTS:All groups reported high baseline symptoms, and levels remained high over time; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormone therapy-exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well-being (eg, survivors with lower vs higher burden scores had 12.4-point higher physical well-being scores). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (P < .005). CONCLUSIONS:Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention.
Project description:Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change.A total of 68 survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) with identified cognitive deficits were randomly assigned to computerized cognitive intervention (male, n = 18; female, n = 16; ALL, n = 23; BT, n = 11; mean age ± standard deviation, 12.21 ± 2.47 years) or waitlist (male, n = 18; female, n = 16; ALL, n = 24; BT, n = 10; median age ± standard deviation, 11.82 ± 2.42 years). Intervention participants were asked to complete 25 training sessions at home with weekly, telephone-based coaching. Cognitive assessments and functional magnetic resonance imaging scans (intervention group) were completed pre- and postintervention, with immediate change in spatial span backward as the primary outcome.Survivors completing the intervention (n = 30; 88%) demonstrated greater improvement than controls on measures of working memory (mean ± SEM; eg, Wechsler Intelligence Scale for Children [fourth edition; WISC-IV] spatial span backward, 3.13 ± 0.58 v 0.75 ± 0.43; P = .002; effect size [ES], 0.84), attention (eg, WISC-IV spatial span forward, 3.30 ± 0.71 v 1.25 ± 0.39; P = .01; ES, 0.65), and processing speed (eg, Conners' Continuous Performance Test hit reaction time, -2.10 ± 1.47 v 2.54 ± 1.25; P = .02; ES, .61) and showed greater reductions in reported executive dysfunction (eg, Conners' Parent Rating Scale III, -6.73 ± 1.51 v 0.41 ± 1.53; P = .002; ES, 0.84). Functional magnetic resonance imaging revealed significant pre- to post-training reduction in activation of left lateral prefrontal and bilateral medial frontal areas.Study findings show computerized cognitive training is feasible and efficacious for childhood cancer survivors, with evidence for training-related neuroplasticity.
Project description:Purpose:To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). Methods:Melanoma survivors were identified within two study populations (N = 104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. Results:Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N = 8), existential problems (N = 2), survivor guilt (N = 2), and posttraumatic stress disorder (N = 6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N = 8), hepatitis (N = 1), colitis (N = 3), and sarcoidosis (N = 1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. Conclusion:A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920.
Project description:The current study investigated the occurrence of emotional distress in parents of long-term survivors of childhood acute lymphoblastic leukemia (ALL) and identified factors associated with parent emotional distress symptoms.Parents of 127 long-term survivors of childhood ALL treated on a chemotherapy-only protocol at St. Jude Children's Research Hospital participated in the study. Parents completed standard ratings of emotional distress, caregiver strain, and child physical, emotional, and psychosocial functioning. Multivariable hierarchical linear regression analyses were used to examine associations between symptoms of caregiver strain, survivor functioning, and parent emotional distress. Covariates included parent education, survivor age, survivor sex, and time since childhood cancer diagnosis.On average, few parents reported significant symptoms of emotional distress. Clinically significant levels of anxiety and depression were reported by 7.1% and 3.1% of parents, respectively. Only 3.9% of parents endorsed significant symptoms of posttraumatic stress. Perceived caregiver strain was significantly associated with symptoms of parent anxiety, depression, and posttraumatic stress. Parent-report of child emotional functioning was significantly associated with symptoms of parent anxiety.Most parents of long-term survivors of ALL exhibit low levels of emotional distress in the context of rates observed in the general population. Perceived caregiver strain was significantly associated with parent emotional distress. Further research is required to examine specific sources of caregiver strain, as well as other risk and protective factors associated with parent emotional distress symptoms.
Project description:Cancer survivors often report cognitive problems. Furthermore, decreases in physical activity typically occur over the course of cancer treatment. Although physical activity benefits cognitive function in noncancer populations, evidence linking physical activity to cognitive function in cancer survivors is limited. In our recent randomized controlled trial, breast cancer survivors who received a yoga intervention had lower fatigue and inflammation following the trial compared with a wait list control group. This secondary analysis of the parent trial addressed yoga's impact on cognitive complaints.Posttreatment stage 0-IIIA breast cancer survivors (n?=?200) were randomized to a 12-week, twice-weekly Hatha yoga intervention or a wait list control group. Participants reported cognitive complaints using the Breast Cancer Prevention Trial Cognitive Problems Scale at baseline, immediately postintervention, and 3-month follow-up.Cognitive complaints did not differ significantly between groups immediately postintervention (p?=?0.250). However, at 3-month follow-up, yoga participants' Breast Cancer Prevention Trial Cognitive Problems Scale scores were an average of 23% lower than wait list participants' scores (p?=?0.003). These group differences in cognitive complaints remained after controlling for psychological distress, fatigue, and sleep quality. Consistent with the primary results, those who practiced yoga more frequently reported significantly fewer cognitive problems at 3-month follow-up than those who practiced less frequently (p?<?0.001).These findings suggest that yoga can effectively reduce breast cancer survivors' cognitive complaints and prompt further research on mind-body and physical activity interventions for improving cancer-related cognitive problems.
Project description:Cognitive dysfunction is a core feature of depression and tends to persist even after mood symptoms recover, leading to detrimental effects on clinical and functional outcomes. However, most currently available treatments have not typically addressed cognition. Modafinil has been shown to have beneficial effects on cognitive function and therefore has the potential to improve cognition in depression. The objective of this double-blind, placebo-controlled study was to investigate the effects of modafinil on cognitive functions in patients with remitted depression.In total, 60 patients with remitted depression participated in the study. Cognitive functions were evaluated with tests of working memory, planning, attention, and episodic memory from the Cambridge Neuropsychological Test Automated Battery at the baseline session and after treatment. A double-blind, randomized, placebo-controlled, parallel groups design was used to assess the effects of single-dose (200 mg) modafinil (n = 30) or placebo (n = 30) on cognition and fatigue. The main outcome measures were neurocognitive test scores from the Cambridge Neuropsychological Test Automated Battery. Visual analogue scales for subjective feelings and fatigue were used as secondary measures.The modafinil group had significantly better performance on tests of episodic memory (p = .01, ?p2 = .10) and working memory (p = .04, ?p2 = .06). Modafinil did not improve planning or sustained attention.This study suggested that modafinil (200 mg) could improve episodic memory and working memory performance in patients with remitted depression. Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.
Project description:Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary intake prior to, during, and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger, or probiotics may improve cancer survivors' energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.
Project description:OBJECTIVES:Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF. METHODS:This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale. RESULTS:A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P?=?0.009), but motor coordination was worse (P?=?0.04). Teachers (P?=?0.04 to P?<?0.0001) and parents (P?=?0.005) reported more executive deficits versus norms, and participants had worse attention (P?=?0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P?=?0.001 to P?<?0.0001) and parent proxy report was lower on the fatigue scales (P?=?0.001 to P?<?0.0001). CONCLUSIONS:Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.
Project description:To examine the bidirectional relationship between parent-child discord and treatment outcome for adolescent treatment-resistant depression.Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or without the addition of cognitive behavior therapy (CBT) in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. The Conflict Behavior Questionnaire was used to assess adolescent (CBQ-A) and parent-reported (CBQ-P) parent-child discord. The impact of remission on parent-child conflict, and the differential impact of medication and CBT on the CBQ-A and CBQ-P, were assessed using generalized linear models.Although there were no differential treatment effects on parent or adolescent-report of conflict, remission was associated with improvement in the CBQ-P. In general, intake family conflict did not predict remission, except in the sub-group of participants whose parents reported clinically significant parent-child conflict at intake, for whom high levels of parent-reported conflict predicted a lower likelihood of remission. Conflict also did not moderate treatment response.Remission of depression may be sufficient to reduce parent-reported parent-child conflict. However, higher parent-reported conflict, in the clinically significant range, predicts a lower likelihood of remission from depression. Clinical trial registration information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902.
Project description:Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov.